Annette Krause

Skin-Sparing Mastectomy with Conservation of the Nipple–Areola Complex and Autologous Reconstruction is an Oncologically Safe Procedure

Objective Is skin-sparing mastectomy (SSM) with conservation of the Nipple–Areola Complex (NAC) and immediate autologous reconstruction as safe in oncologic terms as SSM with resection of the NAC as modified radical mastectomy (MRM)? Summary Background Data The originally described technique of SSM included the removal of gland, NAC, and biopsy scar. However, the risk of tumor involvement of NAC in patients with breast cancer has been overestimated. Patients and Methods Between 1994 and 2000, 286 selected patients with an indication for MRM and tumor margins of greater than 2 cm from the nipple were presented with the alternative of a SSM. Regular follow-up data were evaluable of 112 patients with SSM and 134 patients with MRM. Immediate reconstruction was achieved by latissimus dorsi flap or TRAM flap. The mean follow-up time was 59 (18 to 92) months. Results Patients with SSM were significantly younger than those with MRM but were comparable regarding clinical data, tumor parameters, adjuvant treatment, and overall complications. After intraoperative frozen sections of the NAC-ground, the NAC could be conserved in 61 (54.5%) but was resected in 51 (45.5%) of the 112 patients with SSM. The aesthetic results after SSM were evaluated as excellent or good in 91.1% (102/112) patients and were significantly better after preservation of the NAC (P = 0.001). Six (5.4%) recurrences occurred in 112 patients with SSM compared with 11 (8.2%) cases after MRM. Only 1 recurrence in a conserved nipple was treated by wide excision of nipple with conservation of the areola. This patient is still free of disease after 52 months. Conclusion In patients who are candidates for a mastectomy and tumors distant from the nipple, SSM with intraoperative frozen section of the NAC ground offers the opportunity of NAC conservation without increasing the risk of local recurrences.

The Oncological Safety of Skin Sparing Mastectomy with Conservation of the Nipple-Areola Complex and Autologous Reconstruction : An Extended Follow-Up Study

Objective:To find out if skin sparing mastectomy (SSM) and nipple sparing mastectomy (NSM) with immediate autologous reconstruction as safe in oncological terms as modified radical mastectomy (MRM). Summary Background:The oncological safety of less radical surgical procedures like SSM and NSM cannot be evaluated by randomized trials. A careful and long lasting follow-up of patients, treated with SSM or NSM, is urgently needed. Patients and Methods:Between 1994–2000, 246 selected patients with an indication for MRM were treated with SSM, NSM, or MRM. Short term results were published in 2003.1 After a mean follow-up of 101 months (range 32–126), 238 evaluable patients with SSM (N = 48), NSM (N = 60), or MRM (N = 130) were analyzed for local and distant recurrences, breast cancer specific death, and esthetic results. Results:Local recurrences occurred in 10.4% (SSM), 11.7% (NSM) and 11.5% (MRM) of all patients (P = 0.974). With regard to isolated DM (25.0%, 23.3%, respectively 26.2%; P = 0.916) and breast cancer specific death (20.8%, 21.7%, respectively 21.5%; P = 0.993), there were no significant differences between subgroups. The re-evaluation of esthetic results by surgeons revealed a significant shift from 78.4% excellent results after 59 months to 47.9% after 101 months follow-up (SSM; P = 0.004) and from 73.8% to 51.7% (NSM; P = 0.025). An important risk factor for decreased cosmetic score was application of adjuvant radiotherapy. Conclusion:In patients who are candidates for a mastectomy, skin sparing mastectomy or nipple sparing mastectomy with immediate autologous reconstruction are oncologically safe techniques. Adjuvant radiotherapy decreases the esthetic results even after a longer period of time.

Simultaneous Immunohistochemical Detection of Tumor Cells in Lymph Nodes and Bone Marrow Aspirates in Breast Cancer and Its Correlation With Other Prognostic Factors

PURPOSE We studied the prognostic and predictive value of immunohistochemically detected occult tumor cells (OTCs) in lymph nodes and bone marrow aspirates obtained from node-negative breast cancer patients. All were classified as distant metastases-free using conventional staging methods. PATIENTS AND METHODS A total of 484 patients with pT1-2N0M0 breast cancer and 70 with pT1-2N1M0 breast cancer and a single affected lymph node participated in our trial. Ipsilateral axillary lymph nodes and intraoperatively aspirated bone marrow were examined. All samples were examined for OTCs using monoclonal antibodies to cytokeratins 8, 18, 19. Immunohistological findings were correlated with other prognostic factors. The mean follow-up was 54 +/- 24 months. RESULTS OTCs were detected in 180 (37.2%) of 484 pT1-2N0M0 patients: in the bone marrow of 126 patients (26.0%), in the lymph nodes of 31 patients (6.4%), and in bone marrow and lymph nodes of 23 (4.8%) patients. Of the 70 patients with pT1-2N1MO breast cancer and a single involved lymph node, OTCs were identified in the bone marrow of 26 (37.1%). The ability to detect tumor cells increased with the following tumor features: larger size, poor differentiation, and higher proliferation. Tumors of patients with OTCs more frequently demonstrated lymph node invasion, blood vessel invasion, higher urokinase-type plasminogen activator levels, and increased PAI-1 concentrations. Patients with detected OTCs showed reduced disease-free survival (DFS) and overall survival (OAS) rates that were comparable to those observed in patients who had one positive lymph node. Multivariate analysis of prognostic factors revealed that OTCs, histological grading, and tumor size are significant predictors of DFS; OTCs and grading of OAS. CONCLUSION OTCs detected by simultaneous immunohistochemical analysis of axillary lymph nodes and bone marrow demonstrate independent metastatic pathways. Although OTCs were significantly more frequent in patients with other unfavorable prognostic factors, they were confirmed as an independent prognostic factor for pT1-2N0M0, R0 breast cancer patients.

Effects of Adjuvant Tamoxifen on the Endometrium in Postmenopausal Women With Breast Cancer: A Prospective Long-Term Study Using Transvaginal Ultrasound

PURPOSE To study the value of transvaginal ultrasound (TVS) in endometrial screening of postmenopausal breast cancer patients treated with tamoxifen. PATIENTS AND METHODS In 247 tamoxifen-treated (20 to 30 mg/d for >/= 2 years) women and 98 controls, the endometrium was prospectively followed-up by means of TVS every 6 months for up to 5 years. Patients with homogeneous endometrium of more than 10-mm thickness were then scanned repeatedly every 3 months. RESULTS The mean endometrial thickness was 3.5 +/- 1.1 mm before treatment and increased to a maximum of 9. 2 +/- 5.1 mm after 3 years of tamoxifen application (P: <.0001), which was significantly (P: <.0001) thicker compared with controls. Fifty-two asymptomatic patients with thickened or morphologically suspect endometrium underwent hysteroscopy and dilatation and curettage (D&C), resulting in four uterine perforations. Histopathologically, atrophy was found in 38 patients (73.1%), polyps in nine, hyperplasia in four, and endometrial cancer in one case. In 20 screened patients who reported vaginal bleeding, five atrophies (25%), five polyps, four hyperplasias, and two endometrial cancers were found. Before hysteroscopy and D&C were performed, 36 (69.2%) of 52 asymptomatic and four (20%) of 20 symptomatic patients were scanned by repeated TVS over 2 to 30 months. Invasive diagnostic procedures were significantly (P: <.05) more frequent in younger and obese patients. In the controls, one asymptomatic polyp and one symptomatic hyperplasia were found. CONCLUSION In tamoxifen-treated patients, TVS offered a high false-positive rate, even with a cutoff value of 10 mm for endometrial thickness and repeated TVS scans. Increased iatrogenic morbidity and only one asymptomatic endometrial carcinoma do not warrant endometrial screening by TVS in tamoxifen-treated patients.

Ultrasonographic detection of asymptomatic endometrial cancer in postmenopausal patients offers no prognostic advantage over symptomatic disease discovered by uterine bleeding

The aim of this study was to investigate whether endometrial carcinoma (EC) screening by transvaginal sonography (TVS) has a prognostic advantage over symptomatic EC. In a retrospective study, 190 postmenopausal patients with symptomatic EC and 123 asymptomatic patients with suspicious endometrium detected by TVS were analysed regarding clinical, socio-economic and histopathological findings. Total bleeding time and the International Federation of Gynecology and Obstetrics (FIGO) tumour stage were evaluated with respect to their effect on survival. In 123 asymptomatic patients with suspicious endometrium, 16 (13%) EC, 61 (50%) polyps, 21 (17%) hyperplasias, 23 (19%) atrophias, 1 (0.8%) myoma and 1 (0.8%) metastasis were found. TVS findings in asymptomatic patients resulted in unnecessary operations, which were associated with considerable costs totalling at least 116256. Compared with screened asymptomatic patients, symptomatic patients were significantly (P<0.05) older, more frequently obese, and hypertensive, had a larger proportion of cases living in rural areas and visited their gynaecologists rarely. The bleeding time of symptomatic patients strongly correlated with the tumour stage (P<0.0001). Depending on the bleeding time, the 5-year disease-free survival and overall survival rates were 77% and 86% (no bleeding), 83% and 98% (<8 weeks), 74% and 90% (8-16 weeks), and 62% and 69% (>16 weeks), respectively. The corresponding tumour stage-related data for disease-free and overall survival were 100% (Ia; both rates), 87% and 95% (Ib), 66% and 93% (Ic), 63% and 78% (II) and 36% (III/IV; both rates), respectively. Postmenopausal vaginal bleeding represents an early symptom of EC, but it is not always perceived as problematic by the patients. There is no prognostic advantage for screened compared with symptomatic patients, who had bleeding of shorter than 8 weeks. Moreover, patients who are at a high risk for EC tend to avoid TVS screening. Finally, endometrial screening often results in unnecessary operations, which are associated with increased morbidity and costs.

Anastrozole versus tamoxifen treatment in postmenopausal women with endocrine-responsive breast cancer and tamoxifen-induced endometrial pathology.

PURPOSE: To investigate the effect of switching from adjuvant tamoxifen to anastrozole (Arimidex) treatment in postmenopausal women with endocrine-responsive breast cancer and histologically proven tamoxifen-induced benign endometrial pathology. EXPERIMENTAL DESIGN: Two hundred twenty-six postmenopausal women who had received adjuvant tamoxifen 20 mg/d (> or =12 months, < or =48 months) and developed abnormal vaginal bleeding and/or an asymptomatic endometrial thickness >10 mm [measured by transvaginal ultrasound (TVUS)] were subjected to hysteroscopy and dilation and curettage (D&C). Thereafter, 171 patients were randomized in a phase III study to continue tamoxifen treatment (n = 88) or switch to anastrozole 1 mg/d (n = 83). Patients were monitored for < or =42 months using TVUS at 6-monthly intervals. RESULTS: At study entry, there were no significant differences in vaginal bleeding, endometrial thickness, and histologic findings between the two treatment groups. Throughout the treatment period, there was no significant difference in recurrent vaginal bleeding between groups [anastrozole, 4 of 83 (4.8%); tamoxifen, 9 of 88 (10.2%); P = 0.18]. Six months after randomization, the mean endometrial thickness for patients who switched to anastrozole was significantly reduced compared with those who continued tamoxifen treatment (P < 0.0001). Significantly fewer anastrozole patients required a repeat hysteroscopy and D&C compared with those on tamoxifen [4 of 83 (4.8%) and 29 of 88 (33.0%), respectively; P < 0.0001]. Repeat hysteroscopy and D&C revealed endometrial atrophy in all 4 cases in the anastrozole group and 14 polyps, 8 hyperplasias, and 7 atrophies in the tamoxifen group. CONCLUSIONS: Switching from tamoxifen to anastrozole treatment significantly reduced the need for a second hysteroscopy and D&C due to recurrent vaginal bleeding or thickening of the endometrium in postmenopausal breast cancer patients with tamoxifen-induced endometrial abnormalities.

Simple ovarian cysts in premenopausal patients

Objective: To compare clinical, ultrasonographical, and cytological findings with the histopathological diagnosis of unilocular, anechoic smooth‐walled cystic ovarian tumors (‘simple ovarian cysts’). Method: In 140 premenopausal women simple ovarian cysts were removed by laparoscopy following ultrasound evaluation. In this retrospective study the histopathological diagnosis was correlated with clinical data, sonographic characteristics, macroscopic impression and with cytological findings. Results: Histopathology revealed 21 (15.0%) functional cysts, 31 (22.1%) retention cysts, 9 (6.4%) endometriomas, 3 (2.1%) cystic teratomas, 12 (8.6%) undifferentiated cysts and 64 (45.7%) cystadenomas. No mentionable differences were correlated with the patients age or the size of the cyst as determined by ultrasound. Classically, ‘chocolate‐like’ cystic fluid characterizes endometriomas. However, in the present study cysts with different histopathological classifications exhibited similar fluid characteristics. The cytological diagnosis was correct in only 53 (37.9%) of all 140 cases. Conclusion: In premenopausal women differential diagnosis of ovarian cysts is not possible by clinical characterization, either by ultrasound or cytological evaluation. Simple ovarian cysts should be observed for at least 8 weeks or 2 menstrual cycles, respectively. If persisting over that period, the ovarian cyst should be removed by laparoscopy, but not by cyst aspiration.

Immunohistochemically Detected Lymph-Node Micrometastases in Breast Cancer and their Correlation with Prognostic Factors

Abstract: The prognostic value of immunohistochemically detected micrometastases (N1a‐IHC) in conventionally negative lymph nodes (N0) and its association with newer prognostic factors is controversial.

Differential diagnosis of peri- and postmenopausal ovarian cysts.

OBJECTIVES To test the value of preoperative and intracystic parameters in the differential diagnosis of ovarian cysts. METHODS Criteria for admission of 58 patients were age > 47 years, complete history, detection of CA 125 serum level, and ultrasound findings. Tumor markers (CA 125, cancer-associated serum antigen (CASA), CA 72-4), hormones (estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH)), epidermal growth factor (EGF) receptor and c-erb B-2 amplification rate were detected in cyst fluid. RESULTS Of the 58 subjects, 9 (15.4%) had functional cysts, 37 (63.8%) had benign tumors and 12 (20.8%) had malignant tumors. No functional ovarian cyst presented as echoic or multilocular cyst sonographically. The serum CA 125 values demonstrated significant differences between the non-malignant and malignant patient groups (P < 0.0005). The majority (63.8%, n = 37) of ovarian cysts were obtained at laparotomy, whereas only 36.2% (n = 21) were laparoscopically operated. The cyst fluid levels of FSH (P < 0.005) and LH (P < 0.05) were significantly lower in the functional group than in the benign or malignant group. Malignant cysts were significantly different from non-malignant cysts regarding low E2 (P < 0.01), high FSH (P < 0.05) and CASA (P < 0.02) values. There were no significant correlations between EGF receptor (P = 0.14) and c-erb B-2 (P = 0.06) gene amplification rates and malignant histology. CONCLUSIONS Simple ovarian cysts combined with normal serum CA 125 levels are candidates for conservative follow-up or laparoscopy. The serum CA 125 is a powerful marker for prediction of histology in postmenopausal ovarian cyst. Laparoscopic surgery may be considered in patients with multilocular sonographic findings and normal CA 125 serum level. Combining serum CA 125 levels with cyst fluid parameters (E2, FSH, CASA) improves the sensitivity and specificity in predicting malignancy.

Effectiveness of Trastuzumab (HerceptinTM) in a Patient with Locally Recurrent Breast Cancer after Cardiac Failure Caused by Severe Cytotoxic Pretreatment

In HER2-positive breast cancer patients, the humanized anti-HER-2 monoclonal antibody trastuzumab (HerceptinTM) may improve overall survival. No reports exist regarding the application of trastuzumab in patients with cytotoxically induced cardiac failure and decreased left ventricular ejection fraction or about locally recurrent and advanced disease. In this case report, trastuzumab resulted in a complete and long-lasting response of recurrent and locally advanced breast cancer and was well tolerated in a severely cytotoxically pretreated patient with cardiac failure. We encourage other oncologists to offer trastuzumab also to severely cytotoxically pretreated patients with conditions after cardiac insufficiency or with locally advanced breast cancer.